Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Hypofractionated Image-Guided Radiotherapy For Prostate Cancer: The HEIGHT Trial (HEIGHT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01411332
Recruitment Status : Active, not recruiting
First Posted : August 8, 2011
Results First Posted : July 30, 2021
Last Update Posted : July 30, 2021
Sponsor:
Information provided by (Responsible Party):
Alan Pollack, MD, PhD, University of Miami

Tracking Information
First Submitted Date  ICMJE August 3, 2011
First Posted Date  ICMJE August 8, 2011
Results First Submitted Date  ICMJE May 21, 2021
Results First Posted Date  ICMJE July 30, 2021
Last Update Posted Date July 30, 2021
Actual Study Start Date  ICMJE October 31, 2011
Actual Primary Completion Date July 11, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 11, 2021)
Number of Participants With Biopsy Failure [ Time Frame: Up to 2.25 years ]
Number of participants showing positive prostate biopsy finding post treatment.
Original Primary Outcome Measures  ICMJE
 (submitted: August 5, 2011)
To compare the rate of prostate biopsy positivity after HTIMRT to SIMRT at 2 years after all therapy. [ Time Frame: 2 - 2.5 years post-therapy ]
The proportion of positive biopsy findings among patients without clinical or biochemical failure 2-2.5 years after completing study treatment (RT or ADT, whichever is longer).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 11, 2021)
  • Toxicity Rate [ Time Frame: Up to 6 years ]
    Acute and Late Toxicity will be evaluated by treating physician using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. Acute toxicity will be defined as any treatment related adverse event during and within 3 months of completing treatment. Late Toxicity will be defined as any treatment related adverse events occurring more than 3 months after treatment completion.
  • Mortality [ Time Frame: Up to 6 years ]
    Mortality will be reported as overall survival and failure free survival. Overall survival is defined as the elapsed time from start of radiotherapy to death from any cause. Failure free survival is defined as the elapsed time from start of radiotherapy to first documented evidence of biochemical or clinical failure or death from any cause, whichever occurs first. In the absence of any event defining failure, follow-up time will be censored at the date of last documented failure-free status.
  • Failure Rate [ Time Frame: Up to 6 years ]
    Failure rate will be reported as the incidence of biochemical or clinical failure. Biochemical failure is defined is an increase of 2 or greater from nadir of Prostate Specific Antigen (PSA) levels. Clinical Failure is defined as newly identified extension outside the prostate after initial regression, or urinary obstructive symptoms with carcinoma or regional/distant failure due to radiographic evidence metastasis.
  • Health-Related Quality of Life Scores: EPIC SF-12 [ Time Frame: Up to 6 years ]
    Health-related Quality of Life (HRQOL) will be measured using the Expanded Prostate Cancer Index Composite and Medical Outcomes Study SF-12 (EPIC SF-12) to evaluate patient function and satisfaction after prostate cancer treatment. Response options for each item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better HRQOL.
  • Health-Related Quality of Life Scores: MAX-PC [ Time Frame: Up to 6 years ]
    Health-related quality of life (HRQOL) will be measured using the scores on the Modified 18-item Memorial Anxiety Scale for Prostate Cancer (MAX-PC) from pre-treatment to post-treatment. The scale consists of 18 items (e.g. "I thought about prostate cancer even though I didn't mean to.") scored on a scale from 0 ("not at all") to 3 ("often"). Total scores range from 0 to 54, with higher scores indicating higher levels of anxiety.
  • Biomarker Expression in Prostate Tumor Regions [ Time Frame: Up to 3 years ]
    The amount of biomarker expression will be evaluated via immunohistochemistry (IHC) from ultrasound guided prostate biopsy tissue samples for both functional MRI suspicious regions and those that are not suspicious.
  • Incidence of Circulating Free DNA [ Time Frame: Up to 3 years ]
    As assessed from blood samples
Original Secondary Outcome Measures  ICMJE
 (submitted: August 5, 2011)
  • Number of patients with, and severity of, acute and late adverse events in an HT boost clinical trial. [ Time Frame: 5.25 years ]
    Number of patients with, and severity of, acute and late adverse events in an HT boost clinical trial.
  • To evaluate the influence of HTIMRT to health-related quality of life (HRQOL), prostate cancer-specific anxiety and prostate cancer-specific QOL. [ Time Frame: 5.25 years ]
    Two contemporary instruments (questionnaires) will be utilized to assess patient function and bother (Expanded Prostate Cancer Index Composite-SF12 (EPIC-SF12) and the prostate cancer-specific anxiety Memorial Anxiety Scale for Prostate Cancer patients (MAX-PC).
  • To quantify biomarker expression in different prostate tumor regions, comparing specifically the DCE-MRI enhancing and non-enhancing regions. [ Time Frame: 5.25 years ]
    Quantification of the amount of the biomarker specific immunohistochemical staining in the area of tumor.
  • To evaluate the incidence and relationship of circulating free DNA and tumor cells to tissue biomarkers and prostate biopsy positivity at 2 years after completion of therapy. [ Time Frame: 2 years post-completion of therapy ]
    The investigators test whether absolute pretreatment CTC counts and treatment-induced changes in CTC counts as assessed on our novel microfilter platform correlate with response to therapy (biopsy positivity at two years after treatment).
  • Biochemical failure or clinical failure [ Time Frame: 5.25 years ]
    The cumulative incidence of biochemical or clinical failure allowing for competing risk as needed. Clinical failure is defined as at least a 25% increase in the size of the tumor relative to the smallest volume recorded, or new extension of tumor beyond the capsule, or re-extension of tumor beyond the capsule after initial regression, or urinary obstructive symptoms with carcinoma found at TURP. Biochemical failure is defined as PSA ≥ nadir + 2 ng/mL.
  • Failure-free Survival (FFS) [ Time Frame: 5.25 years ]
    The elapsed time from start of radiotherapy to first documented evidence of biochemical or clinical failure or death from any cause, whichever occurs first. In the absence of any event defining failure, follow-up time will be censored at the date of last documented failure-free status.
  • Overall Survival (OS) [ Time Frame: 5.25 years ]
    The elapsed time from start of radiotherapy to death from any cause. For surviving patients, follow-up will be censored at the date of last contact.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hypofractionated Image-Guided Radiotherapy For Prostate Cancer: The HEIGHT Trial
Official Title  ICMJE A Phase III Trial of Hypofractionated External Beam Image-Guided Highly Targeted Radiotherapy: The HEIGHT Trial
Brief Summary
  1. Delivery of directed hypofractionated targeted (HT) radiotherapy (RT) tumor boost to the dominant tumor lesion in the prostate as identified by multiparametric MRI will increase tumor eradication from the prostate.
  2. Biomarker expression levels differ in the multiparametric MRI defined regions at high risk of harboring tumors that determine outcome.
  3. 10-15% of men undergoing RT have Circulating DNA or tumor cells (CTC) that are related to an adverse treatment outcome.
  4. Quality of life will not differ significantly between the treatment arms.
  5. Prostate cancer-related anxiety will be reduced in the HTIMRT arm, because the patients will be aware that the dominant tumor will be targeted with higher radiation dose.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Prostate Cancer
  • Prostate Adenocarcinoma
Intervention  ICMJE
  • Radiation: SIMRT
    A total dose of 80 Gy will be delivered in 40 fractions to the Clinical Target Volume (CTV).
    Other Name: Standard Fractionated Intensity Modulated Radiotherapy
  • Radiation: HTIMRT
    Dose escalation to the Multiparametric MRI (MP-MRI) by dose painting at 2.35-2.40 Gy per fraction, while the rest of the Clinical Target Volume (CTV) receives 2.0 Gy a fraction to 76 Gy. The hypofractionated targeted (HT) boost region will receive an absolute dose of 89.3-91.2 Gy. Assuming an α/β ratio of 3.0, this would be equivalent to 95.5 Gy in 2.0 Gy fractions.
    Other Name: Hypofractionated Targeted Intensity Modulated Radiotherapy
Study Arms  ICMJE
  • Active Comparator: Arm I: SIMRT
    'Participants in this group will receive the Standard Fractionated Intensity Modulated Radiotherapy (SIMRT) consisting 40 fractions over 8 weeks.
    Intervention: Radiation: SIMRT
  • Active Comparator: Arm II: HTIMRT
    Participants in this group will receive the Hypofractionated Targeted Intensity Modulated Radiotherapy (HTIMRT) consisting of 38 fractions over 7.5 weeks.
    Intervention: Radiation: HTIMRT
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 18, 2017)
19
Original Estimated Enrollment  ICMJE
 (submitted: August 5, 2011)
72
Estimated Study Completion Date  ICMJE December 31, 2021
Actual Primary Completion Date July 11, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • A. Biopsy confirmed adenocarcinoma of the prostate.
  • B. T1-T3a disease based on digital rectal exam.

    1. T1a is permitted if peripheral zone biopsies are positive.
    2. T3a disease based on MRI is acceptable.
  • C. No evidence of metastasis by any clinical criteria or available radiographic tests.
  • D. Gleason score 6-8.
  • E. Patients with Gleason score 8 must be offered long term androgen deprivation therapy (ADT) and refuse such treatment because only 4-6 (±2 months) months (short term ADT) is permitted on this protocol. Gleason score ≥ 8 patients should be recommended to receive short term ADT in conjunction with RT. When given, the ADT recommended to begin after fiducial marker placement, if applicable; however, ADT is permitted to have been started up to two months prior to the signing of consent.

    1. Patients with Gleason score 8 disease must have <40 of the diagnostic tumor tissue involved with tumor.
    2. Patients with Gleason score ≤7 may be treated with 4-6 (±2 months) months of ADT.
  • F. PSA ≤100 ng/mL within 3 months of enrollment. If PSA was above 100 and dropped to ≤100 with antibiotics, this is acceptable for enrollment.
  • G. If PSA is >15 ng/ml or there is ≥ Gleason 8 disease, a bone scan should be obtained ≤4 months before enrollment and should be without evidence of metastasis. A questionable bone scan is acceptable if plain x-rays, CT and/or MRI are negative for metastasis.
  • H. No previous pelvic radiotherapy
  • I. No previous history of radical/total prostatectomy (suprapubic prostatectomy is acceptable)
  • J. No concurrent, active malignancy, other than nonmetastatic skin cancer or early stage chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma). If a prior malignancy is in remission for ≥ 5 years then the patient is eligible.
  • K. Identifiable multiparameter functional MRI defined tumor lesion or lesions using a 1.5T or 3.0T MRI (3.0T preferable), that total in volume <33% of the prostate within 3 months prior to enrollment.

    a. Multiparametric functional including diffusion weighted imaging (DWI) of prostate and pelvis is required prior to protocol consideration

  • L. Ability to understand and the willingness to sign a written informed consent document
  • M. Zubrod performance status <2 (Karnofsky or Eastern Cooperative Oncology Group (ECOG) performance status may be used to estimate Zubrod)
  • N. Willingness to fill out quality of life/psychosocial forms.
  • O. Age ≥35 and ≤85 years.
  • P. Serum testosterone is within 40% of normal assay limits (e.g., x=0.4*lower assay limit and x=.04*upper assay limit + upper assay limit),, taken within 4 months of enrollment. Patients who have been started on ADT prior to signing consent are not required to have a serum testosterone at this level prior to signing consent; but, a serum testosterone prior to fiducial marker placement is recommended.
  • Q. Serum liver function tests (LFTs) taken within 3 months of enrollment.
  • R. Complete blood counts taken within 3 months of enrollment.

Exclusion Criteria

  • A. Previous pelvic radiotherapy.
  • B. Previous history of radical prostatectomy.
  • C. Concurrent, active malignancy, which is not nonmetastatic skin cancer or early stage chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma). If a prior malignancy is in remission for < 5 years then the patient is not eligible
  • D. Not willing to fill out quality of life/psychosocial questionnaires.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 35 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01411332
Other Study ID Numbers  ICMJE 20100635
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Alan Pollack, MD, PhD, University of Miami
Study Sponsor  ICMJE University of Miami
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Alan Pollack, MD, PhD University of Miami
PRS Account University of Miami
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP